The association between mitochondrial DNA copy number, low-density lipoprotein cholesterol, and cardiovascular disease risk
Bibliographic record
Abstract
Abstract Mitochondria are the primary organelle to generate cellular energy. Our group and others have reported that lower mitochondrial DNA copy number (mtDNA CN) is associated with higher risk of cardiovascular disease outcomes (CVD) and higher LDL levels. However, the causal relationship between mtDNA CN and CVD remains to be studied. Here we performed cross-sectional and prospective association analyses of blood-derived mtDNA CN and CVD outcomes in up to 27,316 participants from different racial/ethnic groups with whole genome sequencing. We validated most of the previously reported associations but effect sizes were smaller in this study. For example, one SD unit decrease in mtDNA CN was significantly associated with 1.08-fold (95% CI, 1.04, 1.12; P =1.7E-04) hazard for developing incident coronary heart disease (CHD) adjusting for age, sex and race/ethnicity. We conducted Mendelian randomization (MR) to explore causal relationships between mtDNA CN, LDL, and CHD. Bi-directional univariable MR analyses provided strong evidence indicating higher LDL level is causally associated with lower mtDNA CN, and CHD was weakly associated with lower mtDNA CN. We found no evidence supporting a causal association for lower mtDNA CN with higher CHD risk or higher LDL. In multivariable MR, no associations were observed between mtDNA CN and CHD controlling for LDL level (P =0.92), whereas strong evidence for a direct causal effect was found for higher LDL on lower mtDNA CN, adjusting for CHD status (P =8.3E-10). Findings from this study indicate high LDL underlies the complex relationships between vascular atherosclerosis and lower mtDNA CN.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".